tbuckley/cabot-search huggingface dataset:
Abstract 15503: Myocardial Infarction Increases Diversity of Neutrophil Immunophenotype
Authors: Jonah Stephan, Taylor Zoubul, Robert Brainard, Marcin Wysoczynski
Journal: Circulation (2022)

Background: Following myocardial infarction (MI), immune cells are recruited to clear apoptotic cells and facilitate replacement fibrosis. Neutrophils are the first immune cells recruited, and neutrophilia predicts death and adverse outcomes post-MI. Increased demand for neutrophils is met through emergency granulopoiesis. Methods and Results: Our prior investigations stimulating emergency granulopoiesis with injections of exogenous granulocyte-colony stimulating factor (G-CSF; 100 μg/kg/d) indicated neutrophil immunophenotypic diversity with the emergence of CD101 Neg neutrophils in peripheral blood and spleen. In this study, we tested our hypothesis that MI induced emergency granulopoiesis increases neutrophil phenotypic diversity. We used a non-reperfused MI model in C57BL/6J mice (females, 14-20 wk). At 1, 2, 3, and 7 d post-MI, we harvested bone marrow, peripheral blood, spleens, and hearts. Neutrophil immunophenotypes were quantified in dissociated tissues via flow cytometry. Agreeing with previous findings, neutrophil infiltration of the heart was observed at 1-3 d, reaching a climax at 2 d. Our data demonstrates novel CD101 Neg and CD117 Pos neutrophils present in the heart 1-3 d post-MI (n=3-6, p&lt; 0.05). Additionally, elevated numbers of neutrophils and CD101 Neg neutrophil subtypes were observed in bone marrow, peripheral blood, and spleen relative to naïve mice (n=3-10, p&lt;0.05). Conclusion: We conclude that post-MI production of neutrophils results in the recruitment of diverse neutrophil subtypes to the heart. Future studies will seek to understand how post-MI activation of emergency granulopoiesis instigates neutrophil diversity and how CD101 Neg and CD117 Pos neutrophils are involved in replacement fibrosis. Figure 1. Presence of CD101 Neg and CD117 Pos Neutrophils in the Heart in post-MI. Gating (A-C) and quantification (E-G) of neutrophil immunophenotypes. (n=6-9, Mixed Affects Two-way ANOVA with Multiple Comparisons).
Abstract 15741: Is Home Blood Pressure Monitoring Useful in Diagnosing Hypertension in Young Adults in Primary Care?
Authors: Tomas d Mello, Flora R Campos, Diego Alves Calvão, Rodney Boghossian, Michelle Felipe Falcão, Gabriela Zagni Jardim, Raphaella Ferrão, Luisa Brandão, Giovanna Maselli, Joana Costa, Clara Muguet, Beatriz D Marinho, Ana Cristina Fernandes, Daniela Monteiro, ELIZABETH B MUXFELDT
Journal: Circulation (2022)

Introduction: Recent guidelines have recommended out-of-office blood pressure (BP) measurement to improve the accuracy of the diagnosis of hypertension (HTN) but there are few studies evaluating its use in the younger population and in the scope of primary care. Objective: To assess the degree of agreement between office BP and Home Blood Pressure Monitoring (HBPM), evaluating their use in a young population assisted in primary care. Methods: This is a cross-sectional population study with adults between 20-50 years old registered in the Family Health Strategy. Sociodemographic, anthropometric data and cardiovascular risk factors were recorded. Office BP was the mean of 2 measurements and HBPM followed the 7-day protocol. HBPM &lt; 135 x 85 mmHg and office BP &lt; 140 x 90 mmHg were considered normal while dentifying the 4 phenotypes: Normotension (controlled office BP and HBPM); white-coat HTN (uncontrolled office BP and controlled HBPM); masked HTN (controlled office BP and uncontrolled HBPM) and sustained HTN (uncontrolled office BP and HBPM). Results: 475 individuals were included (male sex: 38%; mean age: 37.6 years ± 8.8 years) of which 93 (20%) had their diagnosis modified after HBPM (43 with white-coat and 47 with masked HTN). Through multiple logistics regression, male gender (OR 3.87: 95%CI 1.70-8.82) was independently correlated with white-coat HTN, while obesity and prehypertension increased the risk of masked HTN by 2 and 5.5 times respectively. Uncontrolled office BP had high specificity (89%) and low sensitivity (49%) for detecting sustained HTN, with a low concordance in the diagnosis of HTN (kappa=0.388). Among men with uncontrolled office BP, 55.6% had a diagnosis of white-coat HTN and among women, 37.1%. Conclusion: HBPM was a useful tool in the diagnosis of hypertension in a young and apparently healthy population in primary care, especially in those with uncontrolled office BP to identify white-coat HTN, and in those with high normal office BP, especially if they were male or obese, for early diagnosis of masked HTN.
Abstract 15758: Association of Socioeconomic, Racial, and Regional Factors in In-Hospital Mortality Among Acute Myocardial Infarction Patients in the United States: A National Analysis of 2.8 Million Admissions
Authors: Olivia Haldenby, Pallav Garg, Shehzad Ali
Journal: Circulation (2022)

Background: Socioeconomic, racial, and regional disparities have been associated with worse clinical outcomes among patients with coronary disease. We evaluated the association of income, race, and geographic variation and in-hospital mortality among acute myocardial infarction (AMI) admissions in the United States. Methods: We conducted a retrospective cohort study using the Nationwide Inpatient Sample from 2015 to 2019. A multi-level logistic regression model was used (with sampling weights) to investigate the association between in-hospital mortality and income quartiles by patient’s ZIP code, race, and hospital regions, while adjusting for hospital clustering, lifestyle factors, clinical history, and hospital-level factors. Results: A total of 2,798,225 hospitalizations (≥18 years) with a principal diagnosis of AMI were identified. In multivariable analysis, compared with the highest income quartile, residents in the lowest income quartile (OR=1.10 [1.08–1.13] P &lt;0.001) or second lowest income quartile (OR=1.07 [1.05–1.09] P &lt;0.001) had higher odds of in-hospital mortality. Compared with those identifying as White, Black (OR=0.89 [0.87–0.91] P &lt;0.001) and Hispanic (OR=0.91 [0.88–0.93] P &lt;0.001) groups had lower odds of mortality, while Asian or Pacific Islander (OR=1.07 [1.03–1.11] P &lt;0.001), Native American (OR=1.11 [1.02–1.21] P &lt;0.05), and Unspecified groups (OR=1.09 [1.05–1.13] P &lt;0.001) had higher odds of mortality. Residents in the South had higher mortality than those in the Northeast (OR=1.06 [1.00–1.12] P &lt;0.05). Conclusion: Our large contemporary study shows that lowest income residents, Whites, Asian or Pacific Islanders, and Native Americans and residents of South had higher in-hospital mortality compared with highest income residents, Blacks and Hispanics, and residents in the Northeast. Additional studies are needed to better understand the complex mechanisms that underpin disparities in outcomes among AMI patients.
Abstract 15745: Effusive Constrictive Pericarditis After Covid-19 Vaccination
Authors: Mouna Penmetsa, Ayesha Shaik, Vidya Nadig
Journal: Circulation (2022)

Case Report: A 42-year-old male with no significant past medical history presented to the emergency department (ED) after a three-week history of myalgias, non-productive cough, and progressively worsening dyspnea accompanied by a two-week history of right-sided chest pain that all started four days after receiving his Pfizer COVID-19 booster vaccine. Chest pain was described as constant, non-radiating, and aggravated by positional changes. On ED arrival, the patient was febrile to 102.9°F and tachycardic with initial labs significant for leukocytosis of 13.6 Thou/uL, C-reactive protein at 17.18 mg/dL, troponins negative x2, and a negative COVID-19 NAAT testing. EKG revealed diffuse T wave inversions and chest x-ray was noncontributory. Transthoracic echocardiogram (TTE) obtained showed a small fibrinous circumferential pericardial effusion with no evidence of cardiac tamponade; however, there was an interventricular septal bounce suggestive of effusive-constrictive pericarditis. This diastolic septal bounce was also seen on cardiac magnetic resonance imaging, along with a pericardial enhancement measuring up to 0.2 cm in thickness. With a negative infectious and autoimmune workup, along with low clinical suspicion for tuberculosis or malignancy, the leading differential was the temporal relationship between receiving the Pfizer COVID-19 mRNA booster vaccine and the development of effusive-constrictive pericarditis (ECP). The patient was started on Colchicine 0.6 mg twice daily, Ibuprofen 400 mg three times daily, and subsequently discharged after symptomatic improvement and being afebrile for 72 hours with plans for close cardiology follow-up. Discussion: ECP is a rare syndrome characterized by a concurrent decrease in pericardial compliance with pericardial effusion and is seen in 4.5% to 6.9% of patients who present with pericardial effusions. To date, less than five other case reports internationally have delineated a relationship between COVID-19 mRNA vaccines and the development of ECP, making recognition of this etiology challenging. In patients who have a mixed hemodynamic picture with subacute features of both cardiac tamponade and constrictive pericarditis, clinicians should have a high index of suspicion for ECP.
Abstract 15712: Imaging Conundrum: The Diagnosis of Unusual Partial Anomalous Pulmonary Venous Return With Dual Connections
Authors: Mariam Baig, JIAFU OU, AMMAR NASIR
Journal: Circulation (2022)

Case: A 68 year old male with a past medical history of hypertension, hyperlipidemia and chronic kidney disease presented for progressive dyspnea on exertion and bilateral lower extremity edema over three weeks. He was found to be in decompensated heart failure and new onset Atrial Flutter with rapid ventricular rate. Transthoracic echocardiography revealed severely impaired left ventricular systolic function with ejection fraction &lt;20%, enlarged right ventricle, moderate right ventricular systolic dysfunction, biatrial enlargement, mild pulmonary hypertension. He was started on guideline directed medical therapy and referred for transesophageal echocardiogram (TEE) with cardioversion for new onset Atrial Flutter and possible tachycardia induced cardiomyopathy. Imaging findings: During TEE, routine doppler of right upper pulmonary vein showed markedly dilated superior vena cava (SVC) (3.6 cm) and unusual predominant outflow with brief mid late systolic inflow (Fig A and B), suggestive of partial anomalous pulmonary venous return (PAPVR). All three other pulmonary veins appeared normal. Also noted to have positive bubble study likely related to PAPVR. Subsequent right heart catheterization left to right shunt with Qp/Qs 1.6, step up noted between SVC and right atrium. CTA revealed partial anomalous right upper lobe pulmonary vein (RUPV) had dual connection to both SVC via window like communication and left atrium (Fig C), no sinus venosus defect seen. Conclusion: This case illustrates an unusual example of PAPVR with bidirectional flow, as well as the importance of thorough evaluation even on routine transesophageal echocardiograms especially for patients with right heart enlargement.
Abstract 15915: Ultrasound Targeted Microbubble Cavitation-Induced Endothelial Hyperpermeability is Calcium-Dependent and Regulated by Enos Signaling
Authors: Anurag N Paranjape, Xucai Chen, Flordeliza S Villanueva
Journal: Circulation (2022)

Introduction: Ultrasound ( US )-targeted microbubble ( MB ) cavitation ( UTMC ) facilitates delivery of cell-impermeant drugs across the endothelial barrier; mechanisms are poorly understood. We reported that UTMC causes inter-endothelial gaps in cultured endothelial cell ( EC ) monolayers, which could increase barrier permeability, and that UTMC increases Ca 2+ influx into ECs. Given that increased intracellular Ca 2+ activates eNOS, and nitric oxide (NO) release promotes microvascular permeability, we hypothesized that UTMC increases intracellular Ca 2+ through activation of mechanosensitive Piezo-1 Ca 2+ channels, leading to NO synthesis and endothelial barrier hyperpermeability. Methods: Transwells were endothelialized with human coronary artery ECs. Lipid MBs were added, and US was delivered for 10 s (1 MHz, 250 kPa, 10 cycles, 10 ms interval). Permeability was measured using dextran transfer and transendothelial electrical resistance ( TEER ). GsMTx4 and L-NAME were used to inhibit Piezo1 and eNOS, respectively; Fluo-4 AM to visualize Ca 2+ influx; DAF-FM to detect NO. S-nitrosylation was measured with biotin switch assay. Results: UTMC reduced TEER (1.7 fold, p&lt;0.05 ) and increased dextran flux across the transwell (2-fold, p&lt;0.01 for 70 kDa dextran, 1.6 fold, p&lt;0.05 for 10 kDa dextran), which was abrogated by L-NAME. UTMC significantly increased Ca 2+ influx into ECs and tripled NO ( p&lt;0.05 ), but these increases and UTMC-mediated hyperpermeability were blunted by Piezo1 channel inhibition ( p&lt;0.0001) . UTMC increased S-nitrosylation of proteins (1.7 fold, p&lt;0.01 ) and was associated with s-nitrosylation of VE-cadherin, its redistribution into focal adhesion junctions, and increased stress fiber formation, which were abolished by L-NAME. Conclusions: UTMC causes endothelial barrier hyperpermeability through a Ca 2+ -dependent mechanism, where Ca 2+ influx into ECs, mediated in part by mechanosensitive Piezo1 channels, modulates eNOS signaling. Our data suggest that eNOS regulates UTMC-induced hyperpermeability, possibly through s-nitrosylation of VE-cadherin. Further studies to examine mechanisms regulating UTMC bioeffects will aid in clinical translation and optimization of UTMC for delivery of cell-impermeant drugs.
Abstract 15845: Microfabricated Anisotropic Tissue Bundles for the Production of 3D Cardiac Tissue at Scale
Authors: Maggie Jewett, Amanda Bluem, Susan Xi, Samuel DePalma, Austin Stis, Brendon Baker
Journal: Circulation (2022)

Rationale: Following myocardial infarct, tissue ischemia and cardiomyocyte (CM) death trigger inflammation followed by extracellular matrix (ECM) remodeling mediated by cardiac fibroblasts (CF). The cardiac tissue engineering field aims to replace damaged myocardium and restore normal cardiac function. The ECM’s high degree of structural anisotropy and the organization of resident cell populations are critical features necessary to recapitulate healthy myocardial function. Thus, there is a critical need for biomanufacturing technologies that can organize ECM and multiple, distinct cell types with microscale precision in tissue grafts of translationally relevant scale. Here, we propose a scalable material strategy for fabricating individual myofiber-like tissues with anisotropic organization and relevant cell populations comparable to native myocardium. Methods and Results: Microchannels of varying widths were perfused with fibrin (20mg/mL fibrinogen with 1U/mL thrombin supplemented with 0.05mg/mL aprotinin for the first 3 days of culture) or a mixture of fibrin and collagen (10mg/ml fibrinogen with 1U/mL thrombin and 2mg/ml collagen). Hydrogels contained up to 40 million/mL cells (25% CFs and 75% CMs) and 8 vol% RGD-functionalized dextran-vinyl sulfone (DVS) electrospun fibers. Microchannel perfusion of composite hydrogel solutions resulted in flow-induced alignment of DVS fibers across all channel sizes (200, 300, 400, and 500 μm), although fiber alignment decreased with increasing channel size. Tissue size, cell spreading, CM contraction, and myofibril development and alignment varied with channel size, cell density, and hydrogel formulation over two weeks inculture. Overall, hydrogel composites with aligned fibers and a combination of CMs and CFs resulted in anisotropic, myofiber-like tissue structures. Conclusion: In this study, we developed a microfabrication approach to produce anisotropic myofiber-like bundles using composites of naturally derived ECM and synthetic polymeric fibers that can be flow-aligned within microfabricated microchannels. This approach allows us to fabricate unit cell tissues of desired size and alignment that can be combined into a larger tissue construct for therapeutic applications.
Abstract 15524: Temporal Changes in the Published Clinical Cardiology Evidence Base
Authors: William Mai, Nikita Jhawar, Guozhan Xie, Fred Kusumoto
Journal: Circulation (2022)

Background and Objective: The published cardiology literature is critical for scientific communication, and we sought to determine if the published clinical cardiology evidence base has evolved over time. Methods: We evaluated the cardiology related publications in the medical journals (M) JAMA (J) and the New England Journal of Medicine (N) and all publications by the specialty journals (CA) Circulation (Ci) and the European Heart Journal (E) in 2000, 2010, and 2020 and added 2001, 2011, and 2021 for JAMA to account for potential annual variability. Results: Publication information is shown in the graph. For the M journals there has been an increase in the percentage of randomized controlled trials (RCT). For the CA journals there has been a significant decrease in single center studies (Si) and a proportionate increase in reanalysis (Re) of data whether from subanalysis of an RCT, registry, or meta-analysis. For CA journals there has been an increase in the size of clinical studies mainly due to the use of larger datasets from registries or claims (Ci: 2000: 4,500/study; 2010: 9,298/study; 2020: 258,725/study and E: 2000: 2,282/study; 2010: 12,652/study; 2020: 249,388/study). CA journals have an increased of studies with patients from multiple continents (Ci: 2000: 5.5%; 2010: 13%; 2020: 35% and E: 2000: 7%; 2010: 14.8%; 2020: 18.8%). There has been an increase in the percentage of clinical studies with documentation of different populations by region or color (In 2020, 58% for all Ci articles and 52% for US and multicontinental EHJ articles), although the number of nonwhites remains small in most studies unless the study was specifically addressing disparities in care. Conclusions: Over the last two decades, the published evidence base has changed with more RCT in the Med journals and more studies that reanalyze large datasets in CA journals. Published studies are now larger, more likely to involve multiple continents, and document population details.
Abstract 15657: Risk Based Scheduling for Pediatric Cardiac Catheterization
Authors: Brian Quinn, Juan Ibla, David Slater, James Thompson, Jessily Ramirez, Paige McAleney, Madison Ramsey, Alexandria Case, Haven Liu, Kathy J Jenkins
Journal: Circulation (2022)

Introduction: Machine learning techniques can predict operational capacity needs and improve understanding of procedural risk in heterogeneous patient populations. Our goal is to combine machine learning and computer simulation to design scheduling formats for pediatric cardiac catheterization maximizing patient safety and system efficiency. Methods: Data for 13,115 pediatric cardiac catheterizations from 2010-19 were used to develop a simulation model including 3 catheterization interventional laboratories. Data on case time, patient and procedural complexity, and adverse events were used to determine statistical distributions on patient, procedure, and system factors for key components of the catheterization lab process. The simulation model was used to evaluate scheduling plans implemented for historical and synthetic populations of patients, comparing both system efficiency and total lab time spent where the system risk of an adverse event is high. Results: A simple scheduling heuristic model was developed where one lab worked cases from lowest to highest risk and another lab worked from highest to lowest risk. This scheduling heuristic was applied to all cases in 2018 and compared against the original schedule. Using thresholds of 10% and 20% probability of an adverse event to separate low, medium- and high-risk times. Implementing the sorting schedule resulted in the reduction of minutes spent at high-risk equivalent to 11.57 days per year. Conclusions: This study demonstrates that predictive analytics and simulation using simple scheduling heuristics results in reduced time at increased risk. Future work includes improving the fidelity of the model to include specific providers, case cancellations, and other system complexities.
Abstract 15528: Indeterminate Cardiomyopathy in a Patient With Birt Hogg Dubé Syndrome and a Clinical Diagnosis of Scleroderma and Prior Atrial Tachy Arrhythmias: A Diagnostic and Therapeutic Dilemma
Authors: Aoife Maher, Brendan F McAdam
Journal: Circulation (2022)

Birt Hogg Dubé (BHD) syndrome, tachycardia induced cardiomyopathy and scleroderma are three well defined diagnoses. A link between them has not been reported. We present a diagnostic and treatment challenge, of a patient with BHD, clinical scleroderma and prior tachycardia induced cardiomyopathy with persistent left ventricular dysfunction despite restoration of sinus rhythm. Mr. X medical history includes recurrent bilateral pneumothoraces and bullectomy, with a cystic lung disease. He was diagnosed with BHD syndrome in 2018. He was diagnosed clinically with scleroderma with myositis based on symptoms and clinical signs with paucity of inflammation on muscle biopsy and negative biomarkers. There has been a limited response to immunosuppressants. In 2020 he presented with symptomatic paroxysmal atrial fibrillation. CMRI showed biventricular dilatation with increased volumes with LVEF of 40%, ​RVEF of 25% in sinus bradycardia. LGE showed subendocardial signal in ​​the basal and mid segment of the lateral and posterolateral walls with small foci of myocardial ​​​signal at the basal and mid inferior RV-LV hinge points. A bespoke CRT-D (secondary to cavity size) was inserted following documented broad complex tachycardia, given the history of reduced ejection fraction despite medical therapy. Right and left heart catheterisations were normal. Endomyocardial biopsy showed no pathological features and no fibrosis or evidence of infiltrative disease. Genotype results are pending. BHD is a genetic disorder, affecting folliculin protein, associated with cystic lesions of the lung, kidney, and skin with an increased risk of renal cell carcinoma (1). There is no known link of BHD syndrome with cardiomyopathy. Studies have demonstrated folliculin has a role in cardiomyocyte generation (2). Given the cardiac biopsy result, not in keeping with scleroderma or tachycardia induced cardiomyopathy, he may have an independent cardiomyopathy, or a first case of cardiomyopathy secondary to BHD. Our challenge continues to be optimising available therapies ensuring the best quality of life, whilst balancing the potential need for cardiac transplant with lifelong immunosuppressant therapy in a condition which has a seven-fold increased risk of renal cancer.